Host factors required for human polyomavirus replication and spread

人类多瘤病毒复制和传播所需的宿主因子

• 批准号: MR/T016493/1
• 负责人: Colin Crump
• 金额: $ 68.71万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT016493%2F1
• 关键词: Host; factors; required; human; polyomavirus

Polyomaviruses are ubiquitous viruses that infect virtually everyone on the planet. We currently know of thirteen different polyomaviruses that infect humans, which are mainly contracted during childhood. These viruses can persist within us for life and they can cause serious problems in immune-suppressed patients, including at least one type of cancer. One of the most significant medical problems that is caused by polyomavirus infection is in kidney transplantation, where a virus known as BK polyomavirus causes extensive damage to the kidneys and bladder. The only available drugs to treat infections with polyomaviruses are either ineffective or can damage the kidneys and so they are not viable options for use in kidney transplant patients, and as a consequence BK polyomavirus infection leads to an unacceptably high risk losing the transplanted kidney. Therefore, we have an urgent need to develop new therapeutics to combat the diseases caused by BK polyomavirus and related viruses. However, there is insufficient knowledge of the basic biology of these viruses.Polyomaviruses express only a handful of their own proteins and so they are particularly reliant on processes within our cells to successfully replicate and spread. We have recently developed large scale genetic screens to identify the genes in our cells that are crucial for BK polyomavirus infection. The proposed research will use state-of-the-art techniques to provide a detailed understanding of what factors within our cells BK polyomavirus needs. This knowledge will identify new ways that we can develop medicines to inhibit these viruses, which could have far reaching benefits for kidney transplant recipients and for treating other diseases caused by polyomaviruses.

多瘤病毒是一种无处不在的病毒，几乎可以感染地球上的每个人。我们目前知道有13种不同的多瘤病毒感染人类，它们主要是在儿童时期感染的。这些病毒可以在我们体内持续存在一生，它们会给免疫抑制的患者带来严重的问题，包括至少一种癌症。由多瘤病毒感染引起的最重要的医学问题之一是肾移植，一种被称为BK多瘤病毒的病毒会对肾脏和膀胱造成广泛的损害。治疗多瘤病毒感染的唯一可用药物要么无效，要么会损害肾脏，因此它们不是肾移植患者的可行选择，因此BK多瘤病毒感染导致失去移植肾脏的风险高得令人无法接受。因此，我们迫切需要开发新的治疗方法来对抗由BK多瘤病毒及相关病毒引起的疾病。然而，对这些病毒的基本生物学知识还不够。多瘤病毒只表达自己的少量蛋白质，因此它们特别依赖于我们细胞内的过程来成功复制和传播。我们最近开发了大规模的基因筛选，以确定我们细胞中对BK多瘤病毒感染至关重要的基因。拟议的研究将使用最先进的技术来详细了解我们细胞内的BK多瘤病毒需要哪些因素。这些知识将为我们开发抑制这些病毒的药物提供新的途径，这可能对肾移植受者和治疗由多瘤病毒引起的其他疾病产生深远的益处。

项目成果

Herpes simplex virus 1 protein pUL21 alters ceramide metabolism by activating the interorganelle transport protein CERT.

• DOI: 10.1016/j.jbc.2022.102589
• 发表时间: 2022-11
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Benedyk, Tomasz H.;Connor, Viv;Caroe, Eve R.;Shamin, Maria;Svergun, Dmitri I.;Deane, Janet E.;Jeffries, Cy M.;Crump, Colin M.;Graham, Stephen C.
• 通讯作者: Graham, Stephen C.

Herpes simplex virus 1 protein pUL21 alters ceramide metabolism by activating the interorganelle transport protein CERT

单纯疱疹病毒1蛋白pUL21通过激活细胞器间转运蛋白CERT改变神经酰胺代谢

• DOI: 10.3204/pubdb-2022-07066
• 发表时间: 2022
• 作者: Benedyk T

Herpes simplex virus 1 protein pUL21 stimulates cellular ceramide transport by activating CERT

• DOI: 10.1101/2022.06.01.494398
• 发表时间: 2022-07
• 期刊: bioRxiv
• 作者: Tomasz H. Benedyk;V. Connor;Eve R. Caroe;M. Shamin;D. Svergun;J. Deane;C. Jeffries;C. Crump;S. C. Graham